ABSTRACT.
Hospital-acquired infections, including surgical site infections (SSIs), pose a concerning challenge because of the growing resistance to multiple drugs, largely influenced by extensive prophylactic antimicrobial therapy. Although SSIs are well documented in advanced hospitals in developed nations, their prevalence and bacterial profiles are inadequately reported in low- and middle-income nations such as Nepal. This retrospective cohort study explored the prevalence of orthopaedic SSIs in relation to bacterial etiology and antimicrobial resistance. We examined the surgical and bacteriological records of patients suffering SSIs (clean or clean-contaminated wounds) within a month of their surgical procedures between January 2020 and June 2022 at the National Trauma Center, Kathmandu, Nepal. The prevalence of orthopaedic SSIs among hospital-visiting patients was 31.2% (448/1,438; 95% CI: 28.8–33.5). There were 341 (76.1%) males and 361 (80.6%) adults with SSIs. Knee/joint infections (n = 141, 31.5%) were predominant. An SSI typically occurs 7 days after surgery. Enterobacterales were dominated by Escherichia coli (n = 54, 40.9%), whereas nonfermenters gram-positive cocci (GPC) were dominated by Pseudomonas aeruginosa (n = 69, 81.2%) and Staphylococcus aureus (n = 216, 93.5%), respectively. Enterobacterales, nonfermenters, and GPC exhibited penicillin resistance at 74.5%, 29.8%, and 65.1%, respectively, whereas cephalosporin resistance was exhibited at 48.3%, 57.1%, and 49.6%; fluoroquinolone resistance at 25.9%, 40.5%, and 25.7%; and aminoglycoside resistance at 21.5%, 43.2%, and 17.3%. One-third of orthopaedic surgeries resulted in SSIs, mainly caused by S. aureus. Fluoroquinolones and aminoglycosides were moderately effective in treating bacterial SSIs, whereas penicillins and cephalosporins were the least effective. Nonfermenters exhibited higher antimicrobial resistance compared with Enterobacterales and GPC.
INTRODUCTION
Modern surgery is plagued by healthcare-associated infections, with prevalence ranging from 5.7% to 19.1% in low- and middle-income countries (LMICs) and 3.6% to 12.0% in high-income countries.1,2 Around 20.0% of these infections are surgical site infections (SSIs), which are ranked second only to respiratory tract infections or urinary tract infections.2
Postoperative infections are common after orthopaedic surgeries,3 resulting in increased morbidity and mortality (one-third of all postoperative deaths), hospitalization duration (by 2 weeks), and healthcare costs (by 300 times).4–9 These infections can occur within 30 days (early cases) or 1 year after surgery (late cases, if implants are used).2,4,6,9 Both preoperative (older age, obesity, tobacco use, underlying diseases, immunosuppressive medications) and perioperative (antibiotic prophylaxis, surgery intervention, length of surgery) factors contribute to orthopaedic SSIs.3,6
The disruption of the immune system in surgical procedures, that is, an intact integumentary system, enables microorganisms, including commensals, to travel either endogenously (the skin, nose, throat, mouth, and intestine) or exogenously (the air, surgical personnel, fomites, and implants).9–11 Microbial virulence, host defenses, and attachment surfaces affect infection progression.8 Planktonic organisms cause localized tissue damage and immune cell lysis upon rapid replication. It may be necessary to remove devitalized tissue and implants surgically if tissue surfaces are compromised by biofilms—polymicrobial communities within a self-secreted matrix.12
The American Society for Health-System Pharmacists recommends perioperative prophylactic antibiotics and intraoperative redosing to prevent SSIs, but there is controversy highlighting irrational antimicrobial use and increasing resistance.11 Antimicrobial resistance has outpaced the development of new antimicrobial agents and is mainly reported in high-income countries, with limited data from LMICs.9 Due to a lack of comprehensive data, the WHO underestimates the prevalence of SSIs in LMICs.6 In Nepal, few studies on this topic exist, leaving the true prevalence of SSIs unknown. We therefore aimed to determine SSI prevalence in orthopaedic patients admitted to a tertiary care orthopaedic hospital in Nepal, as well as the bacterial etiology of these infections and their antimicrobial resistance.
MATERIALS AND METHODS
Study design and settings.
This retrospective cohort study analyzed the data from 1,438 patients who had orthopaedic surgery between January 2020 and June 2022 at the National Trauma Center, Kathmandu, Nepal. Services offered at this 200-bed tertiary care trauma center include general surgery, neurosurgery, spine surgery, burn and plastic surgery, thoracic surgery, and orthopaedics.13 The study protocol was approved by the Institutional Review Committee of the National Academy of Medical Sciences (Ref. No. 684/2079/80). No personal identifiers were collected to maintain data integrity and confidentiality. The ethics committee waived the informed consent requirement.
Inclusion and exclusion criteria.
This study included patients aged 3 to 92 years readmitted after orthopaedic surgery within 48 hours to 30 days due to an SSI. Because of a hospital upgrade to a digital data storage system (MiDas) in 2022, complete entries may have been halted; thus, only April, May, and June of 2022 were included. Excluded patients had presurgery infections, contaminated wounds, postoperative infections after 30 days, or incomplete records of surgical site culture and testing.
Data collection.
The patient information sheet was used to collect the data. Each patient was anonymized with a serial number code. Demographic details, including age and gender, and surgical information, including fracture site, type, postoperative infection duration, wound type (clean or contaminated), bacterial species, and antimicrobial susceptibility testing, were collected. The date (year, month, and day) and time of sample collection were also collected. These details were collected from the hospital database from January 20 to February 27, 2023 and analyzed between March 6 and 28, 2023.
Orthopaedic assessment.
Orthopaedic surgeons examined and performed surgeries on orthopaedic cases, evaluating SSIs by monitoring postoperative symptoms and microbiological findings. The diagnosis was confirmed based on guidelines of the CDC, which includes the date of the event, site of infection, development of purulent discharge, fever, and increased leukocyte counts within 30 days of surgery.14,15 On the basis of the CDC guidelines, SSIs were categorized as (a) superficial incisional SSI that occurs within 30 days after operative procedure where ≥1 incision (superficial incisional primary) or >1 incision (superficial incisional secondary) in the skin and subcutaneous tissue were made; (b) deep incisional SSI manifesting within 30 or 90 days postoperation, affecting the muscle and surrounding soft tissues beneath the incision (≥1 corresponds to deep incisional primary, whereas >1 corresponds to deep incisional secondary); or (c) organ or space SSI that occurs within 30 or 90 days after the operative procedure in any part of the body but the skin, muscle, and surrounding tissue that was involved in the surgery.
Microbiological analysis.
Sample collection and processing.
Surgical wounds were cleaned with 70% ethyl alcohol, and sterile cotton-tipped swabs were collected from viable wound tissue covering a 1.0 cm2 area (deepest parts to avoid superficial commensals). Swabs were then inserted into test tubes containing 0.5 mL of sterile normal saline and sent to the Department of Microbiology within 1 hour for further processing.
Samples were processed according to standard microbiological guidelines.16 A direct Gram stain was performed on the first swab for a presumptive diagnosis. A second swab was inoculated on blood agar and MacConkey agar and incubated for 24 hours at 35 to 37°C. A 48-hour reincubation was done in case no growth occurred. Bacterial pathogens were identified using morphological characteristics and biochemical tests.
Antimicrobial susceptibility testing.
The antimicrobial susceptibility test was conducted using the Kirby–Bauer disc diffusion method and was interpreted using Clinical & Laboratory Standards Institute (CLSI) guidelines (30th edition).17 Colistin and vancomycin susceptibility testing was performed using broth microdilution technique following the CLSI guidelines.18 A methicillin-resistant Staphylococcus aureus (MRSA) strain was defined as S. aureus that was resistant to cefoxitin (a zone size ≤21 mm).17
STATISTICAL ANALYSES
SPSS version 17.0 was used to analyze exported data in Excel version 10.0. Categorical variables were analyzed using frequencies and percentages. Median and interquartile ranges (IQR) of ages and lengths of postoperative infections were calculated. In two groups, independent t tests and χ2 tests were used to compare associations between qualitative and quantitative variables, respectively. P-values <0.05 were considered statistically significant.
RESULTS
Patients’ demographics and SSI prevalence.
Out of 1,438 patients who had orthopaedic surgery, 448 (31.2%) were readmitted with SSIs. The median age of patients with SSIs was 35 years. A total of 361 (80.6%) patients with SSI were adults and 341 (76.1%) were males (Supplementary Table 1).
Year-, season- and month-wise SSI incidences.
Of the 448 SSI cases, 243 (54.2%; P = 0.185) occurred in 2021, and autumn accounted for 134 cases (29.9%; P <0.001). Sixty (13.4%) (P = 0.005) SSIs occurred in November, 53 (11.8%; P = 0.004) in December, and 46 (10.3%; P = 0.065) in September (Supplementary Figure 1).
Fracture sites and associated bacterial species.
A total of 141 (31.5%) knee/leg fractures, 74 (16.5%) wrist/hand fractures, 39 (8.7%) shoulder/arm fractures, and 32 (7.1%) head fractures were associated with SSIs (Supplementary Table 2). Both superficial incisional primary SSIs and organ/space SSIs occurred equally (N = 151, 33.7%). Deep incisional primary SSIs accounted for 62 (13.8%) cases, superficial incisional secondary SSIs for 58 (12.9%) cases, and deep SSIs with deep incisional secondary SSIs for 26 (5.8%) cases. With the exception of superficial incisional secondary SSIs, which were mostly observed in patients who had wrist/hand fractures, all SSIs were mostly observed in patients with knee/leg fractures (Supplementary Table 2). Gram-positive cocci (GPC) accounted for 231 (51.5%) incidences of SSIs, Enterobacterales for 132 (29.5%), and nonfermenters for 85 (19.0%). E. coli (N = 54, 40.9%), Pseudomonas aeruginosa (N = 69, 81.2%), and S. aureus (N = 216, 93.5%) dominated in Enterobacterales, nonfermenters, and GPC, respectively (Supplementary Table 3).
Antimicrobial resistance among the bacterial isolates.
A total of 61.9% (234/378) of the bacterial isolates were resistant to penicillins and 46.4% (391/843) to cephalosporins. Penicillins with β-lactamase inhibitors (17.0%, 59/348) were the least resistant antibiotics. Penicillin resistance was higher in Enterobacterales (74.5%, 35/47) than in nonfermenters (29.8%, 14/47) and GPC (65.1%, 185/284). Enterobacterales, nonfermenters, and GPC exhibited cephalosporins resistance at 48.3% (111/230), 57.1% (4/7), and 49.6% (276/557), respectively, whereas fluoroquinolones resistance was 25.9% (48/185), 40.5% (51/126), and 25.7% (70/272); aminoglycosides resistance was 21.5% (42/195), 43.2% (35/81), and 17.3% (18/104); and penicillins with beta-lactamase inhibitors resistance at 22.7% (25/110), 66.7% (14/21), and 9.2% (20/217) (Table 1).
Table 1.
Antimicrobial resistance among overall bacterial pathogens
| Antibiotics | Total | Resistance | ||||||
|---|---|---|---|---|---|---|---|---|
| n | % | Cumulative % | Enterobacterales | NF | GPC | |||
| Penicillins | P | 11 | 3 | 27.3 | 61.9 | – | – | 3 (27.3) |
| AMP | 78 | 55 | 70.5 | 27 (81.8) | – | 28 (62.2) | ||
| AMX | 55 | 30 | 54.6 | 6 (71.6) | 5 (100.0) | 19 (48.7) | ||
| COX | 189 | 135 | 71.4 | – | – | 135 (71.4) | ||
| CB | 33 | 7 | 21.2 | 1 (50.0) | 6 (19.4) | – | ||
| PI | 12 | 4 | 33.3 | 1 (100.0) | 3 (27.3) | – | ||
| Aminoglycosides | GEN | 249 | 63 | 25.3 | 23.2 | 26 (21.3) | 25 (40.6) | 12 (17.1) |
| AK | 160 | 32 | 20.0 | 16 (19.5) | 10 (66.7) | 6 (17.7) | ||
| Penicillins with β-lactamase inhibitors | AMC | 312 | 37 | 11.9 | 17.0 | 17 (17.0) | – | 20 (9.4) |
| AOX | 11 | 6 | 54.6 | 5 (100.0) | 1 (100.0) | 0 (0.0) | ||
| PIT | 25 | 16 | 64.0 | 3 (60.0) | 13 (65.0) | – | ||
| Fluoroquinolones | CIP | 422 | 115 | 27.6 | 29.0 | 29 (22.7) | 24 (30.0) | 62 (29.0) |
| OF | 81 | 17 | 21.0 | 5 (21.7) | 7 (58.3) | 5 (10.9) | ||
| LF | 80 | 37 | 46.3 | 14 (41.2) | 20 (58.8) | 3 (25.0) | ||
| Cephalosporins | CX | 51 | 25 | 49.0 | 46.4 | – | – | 25 (49.0) |
| CTX | 5 | 2 | 40.0 | 0 (0.0) | – | 2 (50.0) | ||
| CTR | 378 | 123 | 32.5 | 51 (42.2) | – | 72 (32.6) | ||
| CAZ | 11 | 6 | 54.5 | 5 (71.4) | 1 (50.0) | 0 (0.0) | ||
| CPM | 11 | 6 | 54.5 | 1 (33.3) | 3 (60.0) | 2 (66.7) | ||
| CFM | 266 | 176 | 66.2 | 54 (58.1) | – | 122 (76.3) | ||
| CXN | 10 | 1 | 10.0 | 0 (0.0) | – | 1 (20.0) | ||
| CZN | 102 | 50 | 49.0 | – | – | 50 (49.0) | ||
| CT | 9 | 2 | 22.2 | – | – | 2 (22.2) | ||
| Others | AZM | 14 | 10 | 71.4 | – | – | 1 (100.0) | 9 (69.2) |
| COT | 119 | 56 | 47.1 | 30 (48.4) | 8 (57.1) | 18 (41.9) | ||
| DXC | 160 | 45 | 28.1 | – | 3 (100.0) | 42 (26.6) | ||
| IMP | 346 | 57 | 16.5 | 15 (13.5) | 22 (32.8) | 20 (11.9) | ||
| VA | 168 | 58 | 34.5 | – | – | 58 (24.2) | ||
| CL | 180 | 28 | 15.6 | 3 (3.1) | 25 (29.8) | – | ||
AK = amikacin; AMC = amoxicillin clavulanate; AMP = ampicillin; AMX=amoxicillin; AOX = amoxicillin-cloxacillin; AZM = azithromycin; CAZ = ceftazidime; CB = carbenicillin; CFM = cefexime; CIP = ciprofloxacin; CL = colistin; COT = cotrimoxazole; COX = cloxacillin; CPM = cefepime; CT = cefotetan; CTR = ceftriaxone; CTX = cefotaxime; CXN = cephalexin; CZN = cefazolin; DXC = doxycycline; GEN = gentamicin; GPC = gram-positive cocci; IMP = imipenem; LF = levofloxacin; NF = nonfermenters; OF = ofloxacin; PI = piperacillin; PIT = piperacillin tazobactam; P = penicillin; VA = vancomycin.
Table 2 displays the resistance patterns of isolated bacteria. Escherichia coli showed the highest resistance to amoxicillin-cloxacillin (100.0%, 4/4; P = 0.386) and ampicillin (80.7%, 25/31; P = 0.124), moderate resistance to levofloxacin (50.0%, 6/12; P = 0.777) and ceftriaxone (49.0%, 25/51; P = 0.137), and the lowest resistance to amikacin (4.8%, 1/21; P = 0.013). Klebsiella pneumoniae exhibited <50% resistance to all antibiotics except cefixime (61.1%, 11/18), cotrimoxazole (57.7%, 15/26), and piperacillin-tazobactam (66.7%, 2/3). Ciprofloxacin (8.0%, 2/25; P = 0.025) and gentamicin (4.8%, 1/21; P = 0.026) were the least resistant antibiotics against P. vulgaris. Fluoroquinolones, cotrimoxazole, and imipenem were not resistant to Citrobacter freundii. Except for cefixime and penicillin, Serratia marcescens was not resistant to the tested antibiotics (Table 2).
Table 2.
Genus-specific bacterial antimicrobial resistance
| Antibiotics | Gram-Negative Bacilli | Gram-Positive Cocci | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Enterobacterales | Non-Fermenters | |||||||||||
| E. coli (n = 54) | K. pneumoniae (n = 33) | P. vulgaris (n = 25) | C. freundii (n = 11) | Enterobacter spp. (n = 4) | S. marcescens (n = 3) | P. aeruginosa (n = 69) | ACB complex (n = 16) | S. aureus (n = 216) | Streptococcus spp. (n = 8) | CoNS (n = 7) | ||
| Penicillins | P | * | * | * | * | * | * | * | * | 20.0 (2/10) | * | 100.0 (1/1) |
| AMP | 80.7 (25/31) | † | † | † | † | 100.0 (2/2) | † | † | 60.5 (26/43) | * | 100.0 (2/2) | |
| AMX | 62.5 (5/8) | 0.0 (0/1) | 50.0 (1/2) | * | * | * | 100.0 (4/4) | 100.0 (1/1) | 42.9 (15/35) | 100.0 (2/2) | 100.0 (2/2) | |
| COX | * | * | * | * | * | * | * | * | 70.3 (128/182) | 100.0 (3/3) | 100.0 (4/4) | |
| CB | 0.0 (0/1) | * | 100 (1/1) | * | * | * | 19.4 (6/31) | * | * | * | * | |
| PI | 100.0 (1/1) | * | * | * | * | * | 11.1 (1/9) | 100.0 (2/2) | * | * | * | |
| Aminoglycosides | GEN | 32.0 (16/50) | 26.9 (7/26) | 4.8 (1/21) | 10.0 (1/10) | 33.3 (1/3) | 0.0 (0/3) | 31.7 (19/60) | 100.0 (6/6) | 17.2 (11/64) | 0.0 (0/5) | 50.0 (1/1) |
| AK | 4.8 (1/21) | 30.0 (9/30) | 22.2 (4/18) | 12.5 (1/8) | 50.0 (1/2) | 0.0 (0/3) | -a | 66.7 (10/15) | 17.2 (5/29) | 33.3 (1/3) | 0.0 (0/2) | |
| Penicillins with β-lactamase inhibitors | AMC | 17.0 (8/47) | 24.1 (7/29) | 9.5 (2/21) | † | † | 0.0 (0/3) | † | † | 9.6 (19/199) | 12.5 (1/8) | 0.0 (0/5) |
| AOX | 100.0 (4/4) | * | 100.0 (1/1) | * | * | * | 100.0 (1/1) | * | 0.0 (0/5) | * | * | |
| PIT | 100.0 (1/1) | 66.7 (2/3) | 0.0 (0/1) | * | * | * | 61.1 (11/18) | 100.0 (2/2) | * | * | * | |
| Fluoroquinolones | CIP | 32.7 (17/52) | 27.3 (9/33) | 8.0 (2/25) | 0.0 (0/11) | 25.0 (1/4) | 0.0 (0/3) | 26.2 (17/65) | 46.7 (7/15) | 28.1 (57/203) | 57.1 (4/7) | 25.0 (1/4) |
| OF | 23.1 (3/13) | 0.0 (0/3) | 25.0 (1/4) | 0.0 (0/2) | 100.0 (1/1) | 0.0 (0/3) | 44.4 (4/9) | 100.0 (3/3) | 8.3 (3/36) | 12.5 (1/8) | 50.0 (1/2) | |
| LF | 50.0 (6/12) | 33.3 (5/15) | 66.7 (2/3) | 0.0 (0/1) | 50.0 (1/2) | 0.0 (0/1) | 63.0 (17/27) | 42.9 (3/7) | 27.3 (3/11) | 0.0 (0/1) | -a | |
| Cephalosporins | CX | * | * | * | * | * | * | * | * | 43.5 (20/46) | 100.0 (2/2) | 100.0 (3/3) |
| CTX | * | * | 0.0 (0/1) | * | * | * | * | * | 50.0 (2/4) | * | * | |
| CTR | 49.0 (25/51) | 48.3 (14/29) | 25.0 (6/24) | 27.3 (3/11) | 75.0 (3/4) | 0.0 (0/2) | * | * | 30.1 (63/209) | 71.4 (5/7) | 80.0 (4/5) | |
| CAZ | 100.0 (2/2) | 100.0 (3/3) | 0.0 (0/2) | * | * | * | † | 50.0 (1/2) | 0.0 (0/2) | * | * | |
| CPM | 0.0 (0/1) | * | 50.0 (1/2) | * | * | * | 60.0 (3/5) | * | 66.7 (2/3) | * | * | |
| CFM | 62.5 (25/40) | 61.1 (11/18) | 40.0 (8/20) | 7.0 (63.64) | 50.0 (1/2) | 100.0 (2/2) | * | 100.0 (5/5) | 76.0 (117/154) | 100.0 (2/2) | 75.0 (3/4) | |
| CXN | 0.0 (0/2) | 0.0 (0/2) | * | * | * | 0.0 (0/1) | * | * | 20.0 (1/5) | * | * | |
| CZN | * | * | * | * | * | * | * | * | 49.5 (50/101) | 0.0 (0/1) | * | |
| CT | * | * | * | * | * | * | * | * | 12.5 (1/8) | 100.0 (1/1) | * | |
| Others | AZM | * | * | * | * | * | * | 100.0 (1/1) | * | 62.5 (5/8) | 66.7 (2/3) | 100.0 (2/2) |
| COT | 71.4 (10/14) | 57.7 (15/26) | 42.9 (3/7) | 0.0 (0/8) | 50.0 (2/4) | 0.0 (0/3) | † | 57.2 (8/14) | 40.5 (15/37) | 50.0 (1/2) | 50.0 (2/4) | |
| DXC | * | * | * | * | * | * | 100.0 (2/2) | 100.0 (1/1) | 24.8 (37/149) | 83.3 (5/6) | 0.0 (0/2) | |
| IMP | 13.0 (6/46) | 20.0 (5/25) | 8.7 (2/23) | 0.0 (0/10) | 50.0 (2/4) | 0.0 (0/3) | 26.9 (14/52) | 53.3 (8/15) | 10.8 (17/158) | 33.3 (2/6) | 25.0 (1/4) | |
| VA | * | * | * | * | * | * | * | * | 28.3 (52/184) | 8.0 (4/50) | 33.3 (2/6) | |
| CL | 5.9 (3/51) | 0.0 (0/27) | † | 0.0 (0/11) | 0.0 (0/4) | 0.0 (0/3) | 5.0 (7.25) | 20.0 (3/15) | * | * | * | |
ACB complex = Acinetobacter calcoaceticus baumanii complex; AK = amikacin; AMC = amoxicillin clavulanate; AMP = ampicillin; AMX = amoxicillin; AOX = amoxicillin cloxacillin; AZM = azithromycin; CAZ = ceftazidime; CB = carbenicillin; CFM = cefexime; CIP = ciprofloxacin; CL = colistin; CoNS = coagulase-negative Staphylococcus; COT = cotrimoxazole; COX = cloxacillin; CPM = cefepime; CT = cefotetan; CTR = ceftriaxone; CTX = cefotaxime; CX = cefoxitin; CXN=cephalexin; CZN = cefazolin; DXC = doxycycline; E. = Escherichia; GEN = gentamicin; IMP = imipenem; K. = Klebsiella; LF = levofloxacin; OF = ofloxacin; P = penicillin; P. aeruginosa = Pseudomonas aeruginosa; P. vulgaris = Proteus vulgaris; PI = piperacillin; PIT = piperacillin tazobactam; S. = Serratia; VA = vancomycin.
not tested.
intrinsic resistance.
Bold data are statistically significant.
Pseudomonas aeruginosa exhibited 100% resistance to doxycycline, amoxicillin-cloxacillin, and azithromycin. Unlike P. aeruginosa (11.1%, 1/9), Acinetobacter calcoaceticus–Acinetobacter baumannii (ACB) complex showed 100.0% resistance to piperacillin (2/2; P = 0.021). Further, ACB complex exhibited moderate to high resistance to gentamicin (50.0%, 6/12; P = 0.039), amikacin (66.7%, 10/15; P <0.001), and ofloxacin (100.0%, 3/3; P = 0.001). ACB complex (53.3%, 8/15; P <0.001) was twice as resistant to imipenem as P. aeruginosa (26.9%, 14/52; P = 0.030). Both nonfermenters were 100.0% resistant to amoxicillin (Table 2).
Staphylococcus aureus was least resistant to ofloxacin (8.3%, 3/36; P = 0.004), imipenem (10.7%, 17/158; P = 0.008), and cefotetan (12.5%, 1/8) but more resistant to cloxacillin (73.3%, 128/182; P = 0.045) and cefixime (76.0%, 117/154; P = 0.023). A total of 43.5% (20/46; P = 0.009) of S. aureus were MRSA. Coagulase-negative staphylococci (CoNS) exhibited 100% resistance to penicillin, ampicillin, amoxicillin, cloxacillin, and azithromycin. A 100.0% (3/3) incidence of methicillin-resistant CoNS (MRCoNS) was noted (Table 2).
DISCUSSION
Patients undergoing orthopaedic surgeries often experience postoperative infections,4 leading to longer hospital stays and higher treatment costs.2,9 Understanding the antimicrobial resistance of the bacteria causing these infections is crucial for effective treatment.3,8 This study evaluated the prevalence of orthopaedic infections and their resistance to antibiotics in a trauma center in Nepal.
We found a higher prevalence of orthopaedic SSIs than in studies in developed countries (0.8%–9.5%)19,20 but the same as those in LMICs (4.2%–75.0%).5,14 Additionally, different countries in southeast Asia (India, 50.0%–68.0%,9; Bangladesh, 61.8%21; Nepal, 60.6–63.3%22,23) and Africa (Nigeria, 82.0%24; Ethiopia, 71.0%25; and Uganda, 68.8%26) have reported higher infection rates, perhaps as a result of poor infection control practices, untrained staff, prolonged surgery duration, and contaminated wounds being included in their research.4,11
Males (76.1%) and adults (80.6%) had the highest incidence of SSIs in this study, which is in line with the published literature.6,27 The average age of patients with SSIs was 35 years, aligning with the findings of Al-Mulhim et al.7 (38 years). Adults may experience more SSIs as a result of road traffic accidents or wound exposure to the external environment.1 Similarly, male vulnerability to SSIs may be related to higher smoking rates, a well-known risk factor.11 Nevertheless, we found no association between age and SSIs, which is in agreement with other research findings.28,29 This study found that orthopaedic SSIs mostly occurred 7 days after surgery, with knee injuries (31.5%) being the most prevalent, followed by wrist (16.5%) and shoulder (8.7%) injuries. Different studies have found that the time to develop SSIs can vary from 8 days to 8 months, depending on the specific orthopaedic procedure.5,30 As in this study, O’Rourke et al.31 also found higher SSIs after knee surgeries.
In this study, GPC were twice as prevalent as Enterobacterales and thrice as prevalent as nonfermenters. A higher isolation rate of GPC was reported in SSIs in Nepal by Chaudhary et al.27 (58.4%) and Acharya et al.32 (57.1%). There was, however, a study in Bangladesh that reported higher rates of Gram-negative bacteria.21 Staphylococcus aureus (93.5%) dominated GPC in this study, whereas E. coli (40.9%) predominated Enterobacterales and P. aeruginosa (81.2%) predominated nonfermenters. The majority of SSIs were caused by S. aureus (48.2%), with MRSA making up 43.5% of S. aureus. Additionally, 100% incidence of MRCoNS was observed. According to studies, S. aureus makes up 15.0% to 20.0% of SSIs in hospitals,27 overshadowing S. epidermidis and MRSA.10 Notably, MRSA incidence in this study was lower than in a study by Ter Gunne et al.33 (62.0%). In accordance with this study, Abayneh et al.14 reported that E. coli (29.3%), Proteus spp. (14.6%), P. aeruginosa (12.2%), Klebsiella spp. (9.8%), and Citrobacter spp. (7.3%) were the most prevalent organisms responsible for SSIs. In contrast, Zahran et al.1 found that Citrobacter spp. (25.4%) was the most common isolate, followed by Klebsiella spp. (15.9%), E. coli (12.7%), Proteus spp. (12.7%), and Salmonella spp. (12.7%). Direct skin contact or exposure to airborne pathogens might have facilitated their transmission.10
Treating hospital-acquired infections has become increasingly challenging due to the rise of antimicrobial resistance.2,11,34 Compared with Călina et al.,35 bacteria in this study showed higher resistance to penicillins (61.9%) and cephalosporins (51.2%) but lower resistance to penicillins with β-lactamase inhibitors (17.0%). Amoxicillin, cloxacillin, and cefoxitin were 100% resistant against GPC except for S. aureus. Ofloxacin, imipenem, cefotetan, and amoxicillin-clavulanate were the least (<15.0%) resistant to S. aureus, whereas cloxacillin and cefepime were highly (>70%) resistant. Previous studies have also reported similar resistance rates in Gram-positive bacteria.11,22 Several factors, including the presence of modified penicillin-binding proteins (PBP2′ or PBP2a) encoded by mecA, porin loss, and the production of β-lactamase and/or carbapenemase, could contribute to increased β-lactam resistance.1,36 Among Enterobacterales, colistin (3.1%) and imipenem (13.5%) were the most effective drugs. Escherichia coli exhibited >80% resistance to ampicillin, piperacillin, piperacillin-tazobactam, and ceftazidime. More than two-thirds of the K. pneumoniae were resistant to piperacillin-tazobactam and cefepime, whereas one-third were resistant to amikacin and levofloxacin. Hope et al.11 also reported a high resistance to ceftriaxone, cotrimoxazole, gentamicin, and ciprofloxacin among Klebsiella spp. Different studies have shown high resistance to ampicillin, nitrofurantoin, and ceftriaxone in K. pneumonia and attributed this to plasmid-mediated defense mechanisms.1,35 Proteus spp. in this study showed moderate resistance to levofloxacin (66.7%), whereas C. freundii, Enterobacter spp., and S. marcescens showed moderate resistance to cefepime (63.6%), ceftriaxone (75.0%), and ampicillin (100.0%), respectively. Absolute resistance (100%) to cefepime was also observed for Citrobacter spp. by Girma et al.36 Pseudomonas spp. in this study displayed 100% resistance to most β-lactams. Zahran et al.1 and Misha et al.9 also reported 100% resistance of P. aeruginosa to ampicillin, ceftriaxone, ceftazidime, and cephalosporin. The increased resistance may be due to prolonged use of such antibiotics, which may have resulted in bacteria acquiring antibiotic-resistant genes.27 This study highlights the urgent need for stringent antimicrobial stewardship measures to address the imprudent use of antibiotics, poor infection control, and self-treatment practices.1,14
This study had several limitations, including the lack of (a) detection of anaerobes and fungi, (b) multicenter study, (c) inclusion of contaminated wounds, (d) consideration of post-discharge SSIs within 1 year, (e) detection of antimicrobial susceptibility using the broth microdilution technique, and (f) detection of antibiotic-resistance genes. Regardless, this study reports the prevalence of SSIs in orthopaedic wounds, along with the antibiograms and associated antibiotic resistance. In addition to demonstrating high levels of antimicrobial resistance, this study emphasizes the importance of strict antimicrobial stewardship. Healthcare facilities could use these findings to develop intervention and surveillance programs for orthopaedic SSI prevention.
CONCLUSION
There was a high prevalence of orthopaedic SSIs, with an infection onset median of 7 days. Most postoperative infections occur in the knee/leg and wrist/hand. Males and adults were more likely to suffer from SSIs. The predominant pathogens were S. aureus, P. aeruginosa, and E. coli. Staphylococcus aureus, which accounted for nearly 45% of SSIs, was mostly MRSA. Penicillins and cephalosporins were the least effective antibiotics in SSIs, and penicillins with β-lactamase inhibitors, aminoglycosides, and fluoroquinolones were moderately effective.
Supplemental Materials
ACKNOWLEDGMENT
The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.
Note: Supplemental materials appear at www.ajtmh.org.
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